Rotation projects include development of nanobodies for prevention and treatment of mucosal disease (viral and bacteria).
Endowed Chair in Biochemistry and Molecular Biotechnology I
Dr. Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research
Dept of Biochem & Mol Biol And Dept of Chem
Additional information about lab rotations within the CPHR program can be found athttp://www.umassmed.edu/cphr/program/rotations.aspx
Rotation Projects Rotation projects are available to address the following questions: How does the lack of structure in the C-terminal zinc finger of TTP affect the activity of the protein in the cell? In humans, there are three members in the TTP protein family: TTP, TIS11b and TIS11d. Structural studies performed by us and others have shown that while the TZF domain of TTP is partially unstructured in the free state and folds upon binding RNA, those of TIS11d and TIS11b are always folded. We have shown that the degree of structure of the TZF domain affects the activity of the protein in cells and indicates that the protein can modulate its activity through its dynamics. We want to determine whether structural disorder is directly linked to cellular stability or protein localization How do mutations in the RNA-binding domain of TIS11d cause cancer? Several point mutation in TTP and TIS11d have been linked to cancer. In particular, point mutations in the RNA-binding domain of TIS11d are found in leukemia patients. We are currently working on the characterization of the structure, dynamics and biological activity of these mutant proteins to understand their role in the pathogenesis of cancer. How does HuR regulate the stability of its target mRNA? HuR is another protein that, like TTP, binds to AU-rich elements (ARE) in mRNAs and regulate their stability. The detailed mechanisms that determine how HuR regulates transcripts stability are poorly understood. We are investigating how binding or HuR to the 3’UTR of an mRNA leads to its stabilization.
The project aims to develop computational algorithms and software programs for analyzing high-throughput sequence data such as ChIP-Seq RNA-Seq small RNA sequencing data. PhD required. A strong background in computational biology especially experience with analyzing high-throughput sequencing data is highly desirable. Excellent communication and writing skills and the ability to work with experimental and computational collaborators are essential. To apply please forward CV cover letter and three references to: Zhiping.Weng@umassmed.edu
Please contact Dr. Weng for information on rotations that are available in her lab.
Donna M. and Robert J. Manning Chair in Neurosciences
Dr. Brown’s laboratory has focused on the identification of gene defects that elucidate the molecular pathogenesis of selected neuromuscular diseases including amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease), muscular dystrophy, adrenoleukodystrophy, hereditary neuropathy and hyperkalemic periodic paralysis.
The lab is currently looking for motivated postdoctoral scholars with backgrounds in genomics and computational biology. Please email the PI.
Rotation projects are available related to malaria and Burkitt lymphoma. Our projects range from genetic epidemiology to directed genomics studying human, parasite and tumor.
Rotation Projects Rotation projects are available in support of our research. See the research description section of this page.
Rotation projects We apply X-ray crystallography and biochemical methods to understand the mechanisms employed by the ribosome. Potential rotation projects are 1) to understand various aspects of translation via mutagenesis/biochemical assays, 2) to crystallize and work on determining the structures of translation factors and functional ribosome complexes, and 3) to improve computational methods used to determine crystal structures of macromolecules. Feel free to contact the lab for a more detailed discussion.
David J. Freelander Memorial Professor in AIDS Research
Worcester Foundation for Biomedical Research Chair III
Please email Kate.Fitzgerald@umassmed.edu if you are interested in rotations.
Project 1 Investigate the lethal expression of P35 in dam lysogens. Plus inducer No inducer Lysogenic cultures of p35/dam (top) and p35/wildtype (bottom) were diluted and aliquots spotted on media with and without inducer.
UMass Chan Medical School Chair in Biomedical Research
A postdoctoral position is available to study in this laboratory. Contact Dr. Rock for additional details.
Potential Rotation Projects <p >Rotations are available in Dr. Rock’s laboratory for graduate students in the GSBS program. The rotation projects will explore various aspects of how the immune system carries out surveillance to detect viral infections and cancers. Among the potential areas of research are: (1) The alarm signals that alert the immune system to potential danger; (2) The initial innate immune and inflammatory response to infection or other dangerous situations; (3) The biology of the sentinel cells (e.g. dendritic cells) that sense danger and report it the adaptive immune system; (4) The mechanisms by which sentinel cells (e.g. dendritic cells) acquire and display antigens to T cells; and, (5) The antigen presentation pathways by which virally infected or cancer cells display a sampling of their expressed gene products to the activated T cells. Specific rotation projects are chosen based on the student’s interests and state/availability of the various projects in the laboratory. The goals of rotations are for the student to gain knowledge in immunology, to learn how to approach experimental problems, to learn new techniques and methods, and to actually generate data that moves our knowledge forward. In addition, the rotation provides the student the opportunity to evaluate the laboratory as a possible place to conduct their thesis research in the future.
<Long Text /> Potential Rotation Projects Project #1: Probing the structural basis for cooperativity in a dimeric hemoglobin: Scapharca dimeric hemoglobin is an elegantly simple model system for exploring the structural basis for intersubunit communication. Our analysis to date has established a new paradigm for cooperativity in which tightly bound water molecules are used as sensors for ligand state. In this project, the student will first mutate the gene for the native hemoglobin at a residue that is suspected of playing a role in the intersubunit communication. The mutated protein will then be expressed in E. coli and purified and subjected to functional analysis of oxygen binding. Using conditions already established for the native protein, the mutant hemoglobin will then be crystallized and subjected to preliminary x-ray analysis. This project will provide the student with an introduction to two of the most powerful techniques for investigating the structure and function of proteins: site-directed mutagenesis and x-ray crystallography. Additionally, valuable experience in protein purification will be obtained. Project #2: Structural analysis of the polymerization of sickle-cell hemoglobin Sickle cell disease results from the pathological polymerization of deoxygenated hemoglobin S (ß6E->V) within erythrocytes. This polymerization depends upon a complicated interplay of multiple interactions between tetramers. Our high resolution crystal structure of this molecule has elucidated details of some of the important interactions. Several projects are available for rotation students. These include crystallization of sickle-cell hemoglobin in the presence of an inhibitor to identify its binding site, site-directed mutagenesis of hemoglobin S and crystallization of mutants that show altered polymerization characteristics.
Immediate opening! Two postdoctoral positions are available immediately to study cellular andmolecular mechanisms resulting in immunosuppression after alcohol use. Thefocus of this research is the role of monocytes and dendritic cells indecreased antigen-specific T cell activation after alcohol use.Intracellular signalling mechanisms resulting in decreased NF-kBactivation and inflammatory cytokine induction after acute alcoholconsumption are being investigated. Please contact Dr. Szabo for details.
Background for Student Rotation Projects <p >See Politz, Hogan and Pederson (2009) and Politz et al. (2005) in the above list. The novel microRNA work may be the most suitable for student rotations. Potential Rotation Projects <p >Are the nucleolar microRNAs pri-, pre- or mature? <p >Are they complexed with other nucleolar RNAs? <p >Do the cell cycle related proteins in the nucleolus exist as heterotypic complexes? <p >Does the nucleolus of human embryonic stem cells also share these features (which we have so far looked for, and found, only in transformed human cell lines)? <p >Can vanadium tagging be used to detect specific proteins by electron microscopy, perhaps exceeding the limitations of immuno-EM?
Gretchen Stone Cook Chair in Biomedical Sciences
A postdoctoral position is available to study in this laboratory. Contact Dr. Zamore for additional details
Potential Rotation Projects Our laboratory uses a combination of biochemistry, cell biology, and genetics to dissect the RNAi pathway. A rotation project is available to explore the mechanisms that underlie the RNAi phenomenon or the biological pathways in which RNAi enzymes participate in flies, mice and humans.
Postdoctoral positions are available to study the relationship(s) between the Rb/E2F proliferation pathway and p53-dependent apoptosis. Areas of investigation include understanding why E2F1 is unique among the E2F family in its strong apoptosis signaling ability and determining the pathways that lead from E2F1 activation to cell death. Fellows will be associated with a highly motivated and interactive group of researchers studying aspects of cell cycle, apoptosis signaling and cancer using cell culture, virology and animal models. If interested, please contact: Timothy Kowalik Department of Molecular Genetics and Microbiology University of Massachusetts Medical School 55 Lake Avenue North Worcester, MA 01655 The University of Massachusetts Medical School is an Affirmative Action / Equal Opportunity Employer.
Rotation Projects Identify the region on E2F1 responsible for p53-mediated apoptosis. We know that a transcriptionally functional E2F1 is required for apoptosis signaling. We also know that E2F2 does not induce apoptosis in our system. Therefore, domains on E2F1 and E2F2 will be swapped to determine which E2F1 domain is responsible for apoptosis signaling. Role of nuclear kinases in E2F1 mediated apoptosis. Our recent efforts have revealed that E2F1 expression leads to the phosphorylation of p53 and this modification correlates with apoptosis. There are several candidate kinases that need to be analyzed for their contribution to p53 phosphorylation. A dominant negative approach will be used in this project to identify which kinase(s) contribute to the E2F1 signal to p53. Role of CMV IE proteins in proliferation. We have found that both IE1 and IE2 target different Rb family members. IE2 binds to Rb and IE1 interacts with p107. We now know that IE2 is a strong inducer of S phase but IE1 can only significantly modulate proliferation in cells lacking p53. We are interested in knowing why p53 can prevent IE1 from inducing S phase. Mechanism of p53 accumulation by CMV. It has recently been shown that CMV infection results in an accumulation of p53. We have recently found that IE1 expression also leads to p53 accumulation. We wish to determine the steps leading to p53 accumulation and the consequences of this event.
Focus: Cellular and organismal studies of viral infections
Arthur F. Koskinas Chair in Neuroscience
Many rotation projects are available so please inquire.
Arthur F. and Helen P. Koskinas Professor in Biochemistry and Molecular Biotechnology
Postdoctoral Fellow Applications are being accepted for one position. A position is available to develop Cys2His2 zinc finger proteins (ZFPs) for the treatment of monogenic disorders. This project will focus on the creation of ZFPs with novel DNA-binding specificity to recognize sequence elements within genomic loci of therapeutic interest. In collaboration with other laboratories, we will evaluate the activity of these ZFP-based gene therapy reagents in vitro and in vivo in relevant disease models. Applicants will also have the opportunity to learn to apply Cas9 and Cas12a editing systems in vivo.
Potential Rotation Projects Improving the Precision of CRISPR/Cas9 nucleases for gene therapy applications: We are working to improve the precision of the CRISPR/Cas9 system to generate nucleases that will cleave at only a single site in the genome. These engineering efforts focus on increasing the DNA-editing precision of Cas9 and using protein engineering to introduce new properties into the nuclease. Much of this work is now transitioning to the use of Cas9 (and Cas12a) protein-RNA complexes. These modified nucleases will then be applied to patient derived cell-culture systems for the targeted repair or inactivation of disease-causing alleles. With the eventual goal of creating therapeutics for Sickle Cell Disease, beta-Thalassemia, HIV, Limb Girdle Muscular Dystrophy, Hermansky Pudlak Syndrome and other monogenic disorders. ex vivo genome editing in CD34+ HSPCs: We are developing improved Cas9 proteins for delivery ex vivo into CD34+ HSPCs for therapeutic application to sickle cell disease and beta-thalassemia. The goal is to modify the hematopoietic stem cells of a patient to complement the loss of function of the beta-globin gene and then return these cells to the patient through an autologous transplant. Development of Cys2His2 Zinc fingers proteins (ZFPs) as targeted therapeutics: We are developing artificial ZFPs for the regulation of target genes to change their gene expression profiles for therapeutic applications.
A postdoctoral position is available to study in this laboratory. Contact Dr. Lambright for additional details.
Lab Rotations <p >Our lab takes an interdisciplinary approach to the study of fundamental problems in cell biology, signal transduction and membrane trafficking. Rotation projects are available in any of the areas of interest to the lab. Projects are tailored to the individual interests of the students and often involve a combination of molecular, biochemical, biophysical, structural and/or cell based analyses to investigate signaling and trafficking mechanisms. <p >
UMass Memorial Health Care Chair in Biomedical Research
Potential Rotation Projects: Contact Dr. Luzuriaga for project details.
Rotation Project Background
In yeast cells, protein translocation across the endoplasmic reticulum can occur by cotranslational or posttranslational pathways. The objective of this project is to develop a rapid method to inactivate the posttranslational pathway in vivo in yeast cells by appending the CMV-ribosome stalling sequence to the C-terminus of a typical posttranslational translocation substrate (carboxypeptidase Y). Complexes between the posttranslational translocation channel (SEC complex) and the stalled ribosomes will be purified for structural and functional analysis.
A postdoctoral position is available to study in this laboratory. Contact Dr. Craig for additional details.
Potential Rotation Projects Project #1: Lipid-Layer Protein Crystallization for Electron Microscopy.While individual protein molecules can be readily visualized by EM, structural information is greatly enhanced if the molecules can by crystallized into 2-dimensional ordered arrays. Methods for achieving this are well established, making use of lipid monolayers at an air-water interface. Follow literature methods to crystallize "standard" proteins using the lipid-layer method. Observe results by electron microscopy following negative staining. If time permits, carry out preliminary image processing of micrographs and/or crystallization of unknown proteins. Techniques to be learned: lipid layer crystallization methods; grid preparation; use of electron microscope; image processing.
Potential Rotation Projects Several rotation projects are available in structural biology of immune receptors, antigen presentation pathways, T-cell activation, and development of novel T-cell detection reagents. Please see Prof. Stern for details.
A postdoctoral position is available to study in this laboratory. Contact Dr. Gottlinger for additional details.
Potential Rotation Projects 1.The identification of novel binding partners for cellular proteins required for HIV-1 budding using a double tag immunoaffinity purification approach. 2.The characterization of mutant ESCRT-III components that block HIV-1 budding with regard to subcellular localization and their ability to interact with certain phosphoinositol lipids and with other proteins involved in late endosomal sorting. 3.The mapping of binding sites for cellular proteins that we have identified as specific components of HIV-1 using GST pulldown, yeast two-hybrid, and co-immunoprecipitation approaches. 4.The generation and functional characterization of mutant viral Gag proteins that fail to interact with specific cellular partners.
Potential Rotation Projects <p >Our laboratory combines genetic and biochemical approaches to investigate the molecular underpinnings of adaptation. Potential rotation projects are available in two general (and partially overlapping) areas: exploring fitness landscapes through systematic approaches and investigating the molecular mechanism of the Hsp90 chaperone in signal transduction. Please contact the lab to discuss specific rotation projects in more detail.
Population and Quantitative Health Sciences
Focus: The Munro laboratory develops and applies quantitative biophysical approaches to visualize virus replication, and probe the functions of the proteins and RNAs involved.
Focus: Viral entry, antibodies & vaccines, single molecule techniques
Biochemistry and Molecular Biotechnology
Joseph D. Early Chair in Biomedical Research